Modifications, during aging, in the structure and biological integrity of proteins have been well documented and are believed to be involved in a number of devastating age-associated human diseases including Alzheimer's disease and non-insulin-dependent diabetes. A unique strength of the Nathan Shock Center of Excellence at the University of Michigan is that it is home to a group of investigators whose research focuses on molecular aspects of the aging process, who study the origin of structural and functional alterations in proteins during aging, and who seek to explain their role in age-associated diseases. The central goal of the Molecular Spectroscopy and Imaging Core is to provide these Shock Center affiliated investigators with state-of-the-art facilities and instrumentation for the study of aging at the molecular level, to train and assist them in the acquisition of the data, and to ensure that the methodologies are appropriate used and that the data is correctly interpreted. The detailed study of molecular structural alterations requires the use of sophisticated spectroscopic and molecular-imaging and manipulation techniques, which the core provides for its users. Specific aims for the Molecular Spectroscopy and Imaging Core are: 1. To provide facilities, instrumentation and expertise in data collection and analysis to Shock Center investigators who are studying the effects of aging on biomolecular structure, function and interactions. The major emphasis of the core is on laser-based methodologies for optical spectroscopy and imaging of biomolecules 2. To utilize the core's facilities and expertise as a resource that Center investigators can rely on in developing new research initiatives. 3. To facilitate the research emphasis on aging or on age-related diseases by investigators outside the Center and, particularly, in other Shock centers through their utilization of the core facilities in collaborative studies that focus on aging. 4. To respond to arising research needs by developing new innovative methodologies with enhanced sensitivities and resolving power, to adapt them for biomolecular studies, and to make these new tools available to Center researchers for studies of age-related aspects of molecular structure and interactions. In particular, developing the capability to perform single-molecule detection, spectroscopy and manipulation in solution and under physiological conditions, will enable users to study changes in structure and interaction of individual molecules, free of the complications introduced by ensemble-averaging.